Restless Legs Syndrome in NKX2-1-related chorea: An expansion of the disease spectrum

Brain Dev. 2019 Mar;41(3):250-256. doi: 10.1016/j.braindev.2018.10.001. Epub 2018 Oct 21.


Background: Molecular technologies are expanding our knowledge about genetic variability underlying early-onset non-progressive choreic syndromes. Focusing on NKX2-1-related chorea, the clinical phenotype and sleep related disorders have been only partially characterized.

Methods: We propose a retrospective and longitudinal observational study in 7 patients with non-progressive chorea due to NKX2-1 mutations. In all subjects sleep and awake EEG, brain MRI with study of pituitary gland, chest X-rays, endocrinological investigations were performed. Movement disorders, pattern of sleep and related disorders were investigated using structured clinical evaluation and several validated questionnaires.

Results: In patients carrying NKX2-1 mutations, chorea was mainly distributed in the upper limbs and tended to improve with age. All patients presented clinical or subclinical hypothyroidism and delayed motor milestones. Three subjects had symptoms consistent with Restless Legs Syndrome (RLS) that improved with Levodopa.

Conclusions: Patients with NKX2-1 gene mutations should be investigated for RLS, which, similarly to chorea, can sometimes be ameliorated by Levodopa.

Keywords: ADCY5; Benign hereditary chorea; Levodopa; NKX2-1-related chorea; Restless legs syndrome.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Child
  • Child, Preschool
  • Chorea / complications*
  • Chorea / diagnostic imaging
  • Chorea / genetics*
  • Cohort Studies
  • Dopamine Agents / therapeutic use
  • Family Health
  • Female
  • Humans
  • Levodopa / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Pituitary Gland / diagnostic imaging
  • Restless Legs Syndrome / diagnostic imaging
  • Restless Legs Syndrome / drug therapy
  • Restless Legs Syndrome / etiology*
  • Thyroid Nuclear Factor 1 / genetics*


  • Dopamine Agents
  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1
  • Levodopa